Several effective treatments are available for patients with small solitary hepatocellular carcinomas (HCCs). Conversely, the management of patients with large or multinodular HCCs is controversial, and the role of surgical resection is not well defined. Between 2000 and 2006, 51 patients with large or multinodular HCC underwent liver resection. Clinicopathologic and follow-up data were prospectively collected and retrospectively reviewed. The perioperative and long-term outcomes were analyzed. Univariate and multivariate analysis of prognostic factors were conducted. Although 20 patients had multinodular HCCs, 31 had large solitary tumors. Perioperative mortality occurred in eight patients and complications in 15. In patients with large solitary tumors, 5-year disease-free and overall survival were 41.3 per cent and 56.1 per cent, respectively. Those with multinodular HCCs demonstrated 5-year disease-free and overall survival rates of 0 per cent and 33.6 per cent, respectively. Liver resection can result in long-term survival in select patients with large or multinodular HCCs, even in select patients with impaired liver function. Large solitary HCCs seem to have better prognoses than multinodular tumors, with lower recurrence and higher survival rates after surgery. Randomized controlled trials comparing resection to other treatment modalities are indicated to determine optimal patient management.